Circulating tumor cells (CTCs) are cells that are shed by a tumor into the bloodstream and are key mediators of metastasis that can present key information about a patient's disease. CTCs are frequently present in patients with primary and recurrent cancer, and have been found in patients even before a primary tumor was detected by other diagnostic modalities. In addition to early detection, CTC analysis can provide molecular and genetic profiles of both a primary tumor and its metastases, thereby yielding a more complete molecular picture of disease than a tumor biopsy alone and providing a powerful tool for personalized medicine. While circulating tumor DNA (ctDNA) can also provide a genetic profile of cancer, it can be difficult to distinguish from abundant circulating non-tumor DNA and it does not provide the transcriptomic, proteomic, and drug susceptibility information afforded by CTC analysis. However, widespread clinical adoption of CTC analysis for early diagnosis of recurrence and guidance of treatment has been hindered by their rarity in the blood (often ˜1-10 cells per milliliter). CTCs are typically detected at more advanced stages when tumor burden is no longer microscopic and is more difficult to treat, but even then, there are too few CTCs in a typical blood sample to conduct drug susceptibility testing, and the sampling is too sparse for molecular characterization to reflect the heterogeneity of the patient's disease. A larger, more representative CTC sample could be obtained by processing larger blood volumes, but there are practical limits to the amount of blood that can be drawn.
State-of-the-art CTC technologies cannot be easily scaled for higher throughput, for example, the CTC-Chip, FDA-approved CellSearch®, and microfluidic-based immunomagnetic separation technologies, while transformative, require hours to process a few milliliters of blood. Apheresis can process large blood volumes through an extracorporeal circuit, but requires a bulky, expensive setup, constrains patient mobility, and still necessitates considerable post-processing to isolate CTCs. Another method for sampling from large blood volumes introduces an antibody-coated stainless steel rod into a blood vessel for immunocapture of CTCs in flow, but the improvement in CTC yield over a standard blood draw is modest. This is likely due to the short residence time for CTCs to collide with and bind to the rod at normal blood flow velocities. In addition, cells in flow are unlikely to turn their trajectory toward the wire without an additional attractive force, as provided for example by a magnetic technique. Accordingly, new technology and strategies are therefore needed that can rapidly, safely, and effectively interrogate large blood volumes to achieve large-scale CTC enrichment for earlier disease detection and therapy selection.